NM23-H1 expression of head and neck squamous cell carcinoma in association with the response to cisplatin treatment

Yi Fen Wang, Chun Ju Chang*, Jen Hwey Chiu, Chin Ping Lin, Wing Yin Li, Shyue Yih Chang, Pen Yuan Chu, Shyh Kuan Tai, Yu Jen Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We recently reported that low NM23-H1 expression of head and neck squamous cell carcinoma (HNSCC) correlated with poor patients' prognosis. Growing evidence has indicated that high tumor NM23-H1 expression contributes to a good response to chemotherapy. Therefore, we investigated the role of NM23-H1 in susceptibility of HNSCC cells to cisplatin and its clinical significance, as well as the in vitro study for validation was performed. Using immunohistochemistry, we analyzed NM23-H1 expression in surgical specimens from 46 HNSCC patients with cervical metastases receiving surgery and adjuvant chemoradiotherapy. Low tumor NM23-H1 expression correlated with locoregional recurrence of HNSCC following postoperative cisplatin-based therapy (p = 0.056) and poor patient prognosis (p = 0.001). To validate the clinical observation and the effect of NM23-H1 on cisplatin cytotoxicity, we established several stable clones derived from a human HNSCC cell line (SAS) by knockdown and overexpression. Knockdown of NM23-H1 attenuated the chemosensitivity of SAS cells to cisplatin, which was associated with reduced cisplatin-induced S-phase accumulation and downregulation of cyclin E1 and A. Overexpression of NM23-H1 reversed these results, indicating the essential role of NM23-H1 in treatment response to cisplatin. NM23-H1 may participate in HNSCC cell responses to cisplatin and be considered a potential therapeutic target.

Original languageEnglish
Pages (from-to)7392-7405
Number of pages14
JournalOncotarget
Volume5
Issue number17
DOIs
StatePublished - 2014

Keywords

  • Cisplatin
  • Head and neck squamous cell carcinoma (HNSCC)
  • Metastasis
  • NM23-H1
  • Prognosis

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